Medical Specialties Commons^™

Emerging Cellular And Molecular Strategies For Enhancing Central Nervous System (Cns) Remyelination., Mohammad Abu-Rub, Robert H Miller

Anatomy and Regenerative Biology Faculty Publications

Myelination is critical for the normal functioning of the central nervous system (CNS) in vertebrates. Conditions in which the development of myelin is perturbed result in severely compromised individuals often with shorter lifespans, while loss of myelin in the adult results in a variety of functional deficits. Although some form of spontaneous remyelination often takes place, the repair process as a whole often fails. Several lines of evidence suggest it is feasible to develop strategies that enhance the capacity of the CNS to undergo remyelination and potentially reverse functional deficits. Such strategies include cellular therapies using either neural or mesenchymal …

Sptransformer Proteins From The Purple Sea Urchin Opsonize Bacteria, Augment Phagocytosis, And Retard Bacterial Growth, H. Y. Chou, C. Lun, L. C. Smith

Microbiology, Immunology, and Tropical Medicine Faculty Publications

The purple sea urchin, Strongylocentrotus purpuratus, has a complex and robust immune system that is mediated by a number of multi-gene families including the SpTransformer (SpTrf) gene family (formerly Sp185/333). In response to immune challenge from bacteria and various pathogen-associated molecular patterns, the SpTrf genes are up-regulated in sea urchin phagocytes and express a diverse array of SpTrf proteins. We show here that SpTrf proteins from coelomocytes and isolated by nickel affinity (cNi-SpTrf) bind to Gram-positive and Gram-negative bacteria and to Baker’s yeast, Saccharomyces cerevisiae, with saturable kinetics and specificity. cNi-SpTrf opsonization of the marine bacteria, Vibrio diazotrophicus, augments phagocytosis, …

Epha2/Ephrin-A1 Mediate Corneal Epithelial Cell Compartmentalization Via Adam10 Regulation Of Egfr Signaling., Nihal Kaplan, Rosa Ventrella, Han Peng, Sonali Pal-Ghosh, Constadina Arvanitis, Joshua Z Rappoport, Brian J Mitchell, Mary Ann Stepp, Robert M Lavker, Spiro Getsios

Anatomy and Regenerative Biology Faculty Publications

Purpose: Progenitor cells of the limbal epithelium reside in a discrete area peripheral to the more differentiated corneal epithelium and maintain tissue homeostasis. What regulates the limbal-corneal epithelial boundary is a major unanswered question. Ephrin-A1 ligand is enriched in the limbal epithelium, whereas EphA2 receptor is concentrated in the corneal epithelium. This reciprocal pattern led us to assess the role of ephrin-A1 and EphA2 in limbal-corneal epithelial boundary organization.

Methods: EphA2-expressing corneal epithelial cells engineered to express ephrin-A1 were used to study boundary formation in vitro in a manner that mimicked the relative abundance of these juxtamembrane signaling proteins in …

Embryonic Transcription Factor Expression In Mice Predicts Medial Amygdala Neuronal Identity And Sex-Specific Responses To Innate Behavioral Cues., Julieta E Lischinsky, Katie Sokolowski, Li Peijun, Shigeyuki Esumi, Yasmin Kamal, Meredith Goodrich, Livio Oboti, Timothy R Hammond, Meera Krishnamoorthy, Daniel Feldman, Molly Huntsman, Judy Liu, Joshua G Corbin

Pediatrics Faculty Publications

The medial subnucleus of the amygdala (MeA) plays a central role in processing sensory cues required for innate behaviors. However, whether there is a link between developmental programs and the emergence of inborn behaviors remains unknown. Our previous studies revealed that the telencephalic preoptic area (POA) embryonic niche is a novel source of MeA destined progenitors. Here, we show that the POA is comprised of distinct progenitor pools complementarily marked by the transcription factors Dbx1 and Foxp2. As determined by molecular and electrophysiological criteria this embryonic parcellation predicts postnatal MeA inhibitory neuronal subtype identity. We further find that Dbx1-derived and …

Bilayered, Non-Cross-Linked Collagen Matrix For Regeneration Of Facial Defects After Skin Cancer Removal: A New Perspective For Biomaterial-Based Tissue Reconstruction, Shahram Ghanaat, Adorjan Kovacs, Mike Barbeck, Jonas Lorenz, Anna Teiler, Nader Sadeghi, Charles Kirkpatrick, Robert Sader

Surgery Faculty Publications

Classically skin defects are covered by split thickness skin grafts or by means of local or regional skin flaps. In the presented case series for the first time a bilayered, non-crossed-linked collagen matrix has been used in an off-label fashion in order to reconstruct facial skin defects following different types of skin cancer resection. The material is of porcine origin and consists of a spongy and a compact layer. The ratio of the two layers is 1:3 in favour of the spongy layer. The aim of the study was to investigate the potential of this matrix for skin regeneration as …

Genetic Modification Of Human Mesenchymal Stem Cells Helps To Reduce Adiposity And Improve Glucose Tolerance In An Obese Diabetic Mouse Model., Sabyasachi Sen, Cleyton C Domingues, Carol Rouphael, Cyril Chou, Chul Kim, Nagendra Yadava

Medicine Faculty Publications

INTRODUCTION: Human mesenchymal stem cells (MSCs) are multipotent cells that can differentiate into fat, muscle, bone and cartilage cells. Exposure of subcutaneous abdominal adipose tissue derived AD-MSCs to high glucose (HG) leads to superoxide accumulation and up-regulation of inflammatory molecules. Our aim was to inquire how HG exposure affects MSCs differentiation and whether the mechanism is reversible.

METHODS: We exposed human adipose tissue derived MSCs to HG (25 mM) and compared it to normal glucose (NG, 5.5 mM) exposed cells at 7, 10 and 14 days. We examined mitochondrial superoxide accumulation (Mitosox-Red), cellular oxygen consumption rate (OCR, Seahorse) and gene …

Targeting Il13ralpha2 Activates Stat6-Tp63 Pathway To Suppress Breast Cancer Lung Metastasis, Panagiotis Papageorgis, Sait Ozturk, Arthur W. Lambert, Christiana M. Neophytou, Alexandros Tzatsos, Chen K. Wong, Sam Thiagalingam, Andreas I. Constantinou

Anatomy and Regenerative Biology Faculty Publications

Introduction

Basal-like breast cancer (BLBC) is an aggressive subtype often characterized by distant metastasis, poor patient prognosis, and limited treatment options. Therefore, the discovery of alternative targets to restrain its metastatic potential is urgently needed. In this study, we aimed to identify novel genes that drive metastasis of BLBC and to elucidate the underlying mechanisms of action.

Methods

An unbiased approach using gene expression profiling of a BLBC progression model and in silicoleveraging of pre-existing tumor transcriptomes were used to uncover metastasis-promoting genes. Lentiviral-mediated knockdown of interleukin-13 receptor alpha 2 (IL13Ralpha2) coupled with whole-body in vivo bioluminescence imaging was …

Klf4-Sqstm1/P62-Associated Prosurvival Autophagy Contributes To Carfilzomib Resistance In Multiple Myeloma Models., Irene Riz, Teresa S. Hawley, Robert G. Hawley

Anatomy and Regenerative Biology Faculty Publications

Multiple myeloma (MM) is an incurable clonal plasma cell malignancy. Because of a high rate of immunoglobulin synthesis, the endoplasmic reticulum of MM cells is subjected to elevated basal levels of stress. Consequently, proteasome inhibitors, which exacerbate this stress by inhibiting ubiquitin-proteasome-mediated protein degradation, are an important new class of chemotherapeutic agents being used to combat this disease. However, MM cells still develop resistance to proteasome inhibitors such as carfilzomib. Toward this end, we have established carfilzomib-resistant derivatives of MM cell lines. We found that resistance to carfilzomib was associated with elevated levels of prosurvival autophagy, and Kruppel-like factor 4 …

Medical Students In Microscopic Anatomy And Pathology Laboratories: Design Of An E-Learning Histology And Histopathology Atlas As An Evolving Response To Interdisciplinary Pre-Clinical Curricular Needs, Michelle S. Davis, Alexandra Mills, Gisela Butera, Donald S. Karcher, Patricia S. Latham, Janette Krum, Rosalyn A. Jurjus

Anatomy and Regenerative Biology Faculty Publications

E-learning, also known as computer-assisted learning, successfully bridges anatomical knowledge and transferrable skills, such as critical analysis, teamwork, leadership and communication. Several institutions have already integrated histology and physiology in team based laboratory approaches, but integration of histology and pathology instruction has been done to a lesser extent. Our aim was to develop an e-learning atlas that integrates microanatomy and pathology laboratory for an interdisciplinary pre-clinical medical curriculum.

A multidisciplinary team of teaching faculty and students developed an online atlas (microanatomyatlas.com) that includes a library of histology and histopathology images. Traditional laboratory manual instructions and study objectives were added onto …

Improving Anatomical Knowledge Through Interactive Modules On The Ob/Gyn Clinical Clerkship, Artin Galoosian, Jill A. Krapf, Kirsten Brown, Gisela Butera, Ellen F. Goldman, Rosalyn A. Jurjus

Anatomy and Regenerative Biology Faculty Posters and Presentations

The goal of this study is to evaluate the impact of a newly designed interactive method of teaching clinically relevant anatomy to medical students on the OB/GYN clerkship. A 20-question multiple-choice exam was administered to 143 consenting third-year medical students at the beginning and end of each OB/GYN rotation. Students participated in a skills lab with preparatory e-modules that linked anatomy to clinical applications during each rotation. Topics included perineal muscle anatomy (laceration), anterior abdominal wall anatomy (cesarean section), vulvovaginal and uterine anatomy (IUD), and pelvic organ, vasculature, and neural anatomy (hysterectomy). Mean scores improved significantly after the nesting of …

Improving Anatomical Knowledge Retention In Medical Students Entering The Surgery And Obstetrics And Gynecology Clinical Rotations By Nesting Interactive Modules, Samantha Ahle, Jill Krapf, Kirsten Marie Brown, Juliet Lee, Gisela Butera, Ellen Goldman, Myriam Ferzli, Rosalyn A. Jurjus

GW Research Days 2014

Background: It is well documented in the medical education literature that students retain minimal anatomy knowledge when transitioning from pre-clinical didactics to clinical application on the wards. In a previous study at our own institution we were able to quantify this knowledge deficit in students on surgical clerkships, specifically surgery and obstetrics and gynecology (OB/GYN). Using our previous data, we designed an integrated, nested clinical teaching model utilizing e-modules to review clinically relevant surgical anatomy during their clinical rotations.

Objective: The goal of this study is to evaluate the impact of a newly designed method of teaching clinically relevant anatomy …

The Cancer Stem Cell Conundrum In Multiple Myeloma, Robert G. Hawley

Anatomy and Regenerative Biology Faculty Publications

No abstract provided.

Melanoma Induction By Ultraviolet A But Not Ultraviolet B Radiation Requires Melanin Pigment, Frances P. Noonan, M. Raza Zaidi, Agnieszka Wolnicka-Glubisz, Miriam R. Anver, Jesse Bahn, Anastas Popratiloff, +9 Additional Authors

Anatomy and Regenerative Biology Faculty Publications

Malignant melanoma of the skin (CMM) is associated with ultraviolet radiation exposure, but the mechanisms and even the wavelengths responsible are unclear. Here we use a mammalian model to investigate melanoma formed in response to precise spectrally defined ultraviolet wavelengths and biologically relevant doses. We show that melanoma induction by ultraviolet A (320–400 nm) requires the presence of melanin pigment and is associated with oxidative DNA damage within melanocytes. In contrast, ultraviolet B radiation (280–320 nm) initiates melanoma in a pigment-independent manner associated with direct ultraviolet B DNA damage. Thus, we identified two ultraviolet wavelength-dependent pathways for the induction of …

Targeting The Cancer Cell Cycle By Cold Atmospheric Plasma, Olga Volotskova, Teresa S. Hawley, Mary Ann Stepp, Michael Keidar

Anatomy and Regenerative Biology Faculty Publications

Cold atmospheric plasma (CAP), a technology based on quasi-neutral ionized gas at low temperatures, is currently being evaluated as a new highly selective alternative addition to existing cancer therapies. Here, we present a first attempt to identify the mechanism of CAP action. CAP induced a robust ~2-fold G2/M increase in two different types of cancer cells with different degrees of tumorigenicity. We hypothesize that the increased sensitivity of cancer cells to CAP treatment is caused by differences in the distribution of cancer cells and normal cells within the cell cycle. The expression of γH2A.X (pSer139), an oxidative stress reporter indicating …